The generation of B cell diversity in mice will be analyzed in two ways. Firstly, the biochemical nature and structure of pre-B cell IgM will be determined by constructing pre-B cell hybridomas from fetal liver. Evidence has already been obtained using such hybridomas that there is asynchronous onset of immunoglobulin chain synthesis and that pre-B cells synthesize micron heavy chains but no light chains. The large amounts of immunoglobulin obtained from such hybridomas are being used to study VH diversity by isoelectric focussing and amino acid sequencing. A second set of experiments are being directed to elucidation of the generation of isotypic diversity among surface immunoglobulin positive lymphocytes. For these experiments cellular aspects of LPS mediated induction of IgG and IgA expression by IgM bearing precursors will be studied in vitro. The effects of metabolic inhibitors and other regulatory cells on differentiation of plasma cells will be studied.